Asthma is a chronic inflammatory disease of the airways, in which many inflammatory genes are overexpressed. Transcription factor, nuclear factor-kappaB (NF-kappaB), which is thought to control the ... [more ▼]

Asthma is a chronic inflammatory disease of the airways, in which many inflammatory genes are overexpressed. Transcription factor, nuclear factor-kappaB (NF-kappaB), which is thought to control the transcriptional initiation of inflammatory genes, has been poorly investigated in asthma. In the present report, bronchial cells (BCs), recovered by bronchial brushing in healthy and heaves-affected horses (i.e., an animal model of asthma), were assessed for NF-kappaB activity. Small amounts of active NF-kappaB were present in BCs of healthy horses, whereas high levels of NF-kappaB activity was found during crisis (i.e., acute airway obstruction) in all heaves-affected horses. Three weeks after the crisis, the level of NF-kappaB activity found in BCs of heaves-affected horses was highly correlated (p < 0.01) to the degree of residual lung dysfunction. Unexpectedly, active NF- kappaB complexes found in BCs of heaves-affected horses were mainly p65 homodimers, rather than classic p65-p50 heterodimers. At last, intercellular adhesion molecule-1 (ICAM-1) expression paralleled p65 homodimers activity in these cells. These results demonstrate that the kinetics of NF-kappaB activity is strongly related to the course of the disease and confirm the relevance of NF-kappaB as a putative target in asthma therapy. Moreover, uncommon p65 homodimers could transactivate, in BCs, a subset of genes, such as ICAM-1, characteristic of chronic airway inflammation. [less ▲]

The presence of chymase-like proteinase in bovine mast cells was investigated by an enzyme-histochemical technique (naphthol-AS-D-chloroacetate as substrate) in normal skin, primary bronchus, lung and ... [more ▼]

The presence of chymase-like proteinase in bovine mast cells was investigated by an enzyme-histochemical technique (naphthol-AS-D-chloroacetate as substrate) in normal skin, primary bronchus, lung and duodenum. The counts and distribution of chymase-positive and toluidine blue-positive mast cells were compared by means of successive staining. Mast cells with chymase-like activity were detected in all areas, but their proportion was greater in connective than mucosal tissues, with the exception of the skin. These results contrast with those obtained in rodents, in which chymase-like proteinases are detected in all tissues and also in all mast cells. Bovine mast cells are closer to those of human beings, in which chymase-containing mast cells predominate in connective tissues, including skin. The results suggest that more than one chymase subset is present, at least in duodenum. The possible occurrence of dual-specific chymase mast cells, as in other ruminants, is discussed. [less ▲]

Juvenile nephropathy was diagnosed in a Boxer, a Rottweiler, a Collie and an Irish Wolfhound dog, each presenting with signs compatible with chronic renal failure. The diagnosis in each case was based on ... [more ▼]

Juvenile nephropathy was diagnosed in a Boxer, a Rottweiler, a Collie and an Irish Wolfhound dog, each presenting with signs compatible with chronic renal failure. The diagnosis in each case was based on the presence of persistence of poorly differentiated tissue (immature glomeruli and/or tubules, persistent mesenchyme) on histopathologic examination. Although juvenile nephropathy has been reported in many breeds of dog, this is the first report of the condition in the Collie and the Irish Wolfhound and only the second description in the Boxer and the Rottweiler. The possibility of an inherited origin of the condition in these four breeds is at present unknown. [less ▲]

The cardiovascular response to 5-hydroxytryptamine (5-HT) challenge has been previously described in cattle. Abrupt bradycardia, followed by tachycardia, triphasic systemic blood pressure response, and ... [more ▼]

The cardiovascular response to 5-hydroxytryptamine (5-HT) challenge has been previously described in cattle. Abrupt bradycardia, followed by tachycardia, triphasic systemic blood pressure response, and pulmonary hypertension were the major changes elicited by 5-HT. The purpose of the present study was to determine whether the cardiovascular response to 5-HT in calves was attributable to 5-HT2 receptors. A specific 5-HT2 antagonist (metrenperone, 0.05 mg/kg) was administered intramuscular to six unsedated Friesian calves 30 min before the animals were given a 5-min intravenous 5-HT infusion. Mean systemic arterial (SAP), mean pulmonary arterial (PAP), pulmonary capillary wedge (PW) pressures were obtained by means of fluid-filled catheters, and cardiac output (CO) was measured by the thermodilution technique. Heart rate, stroke volume, systemic (SVR) and pulmonary (PVR) vascular resistances were calculated. Administration of 5-HT after metrenperone induced a short-lasting period of severe bradycardia followed by tachycardia and increased CO. The systemic blood pressure response was exclusively hypotensive and associated with a decrease in SVR. Conversely, PAP, PW, and PVR were not modified by 5-HT administration. The results establish that 5-HT induced systemic as well as pulmonary hypertension is mediated through the activation of type-2 serotonergic or alpha-adrenergic receptors, or both. In contrast, neither apnoea, bradycardia and hypotension, nor the positive chronotropic effect induced by 5-HT in cattle are mediated through such receptors. [less ▲]

A case of concurrent canine systemic lupus erythematosus (SLE) and generalized bacterial infection in a six-year-old female Beauceron is reported. The dog presented with purulent nasal and ocular discharges, skin lesions (including seborrhea, hyperkeratotic areas, and papules as well as ecchymoses around the eyes, on both sides of the pinnae, and on the vulva), generalized lymph node enlargement, a mitral murmur, and lameness. Later, facial swelling, a retrobulbar abscess, and a cough also developed. Occurrence of a generalized bacterial infection was established by culture of group-C, beta-hemolytic Streptococcus from the throat, the mouth, a biopsy site (popliteal lymph node area), the retrobulbar abscess, and the lung. The diagnosis of SLE was based on the clinical signs and particularly on the occurrence of antinuclear antibody (ANA) and antidoublestranded-desoxyribonucleic acid (ds-DNA) antibody. Interestingly, the latter type of antibodies were also detected in two young female puppies whelped by this dog. Salient histological findings included an extreme cell depletion of the lymph nodes and spleen and severe pneumonitis and peribronchiolitis. The results of this case indicate that a definite diagnosis of canine SLE can, at times, be made on the basis of the presence of serum ANA and ds-DNA antibodies. [less ▲]

Mast cell (MC) phenotypes may vary with respect to tissue site, sensitivity to degranulating agents, dependency on T lymphocytes and, above all, the composition of their granules. Proteinases (either trypsin-like or chymotrypsin-like) are granule constituents which provide an important means of distinguishing subtypes of MCs in man and rodents. The purpose of this study was to compare the distribution of MC trypsin-like protease (tryptase) in a variety of bovine tissues with the aim of examining MC heterogeneity. Tryptase was found in MCs regardless of their location within tissues. With respect to tryptase content, bovine MC distribution resembled more that of human and canine tissues than that of mice and rats. Comparison of the results yielded by enzyme- and immuno-histochemical staining suggested that a tryptase-negative, dual-specific chymase-positive MC subset occurred, at least in duodenal lamina propria, around bronchioles and within alveolar septa. The study also suggested that monoclonal antibodies raised against human tryptase can be used for quantitation of bovine tryptase in biological fluids; this offers a promising tool for evaluating the role of MC activation in disease. [less ▲]

In order to define a reliable method for estimating maximal ventilation in cattle, 12 healthy calves underwent a rebreathing trial and injections of increasing doses of lobeline, a respiratory analeptic ... [more ▼]

In order to define a reliable method for estimating maximal ventilation in cattle, 12 healthy calves underwent a rebreathing trial and injections of increasing doses of lobeline, a respiratory analeptic. The effects of these tests on the main ventilatory parameters (tidal volume, VT; respiratory frequency, fR and minute volume,.VE) recorded during the 15 s of maximal response were studied and compared. The sharp rise in.VE(4.8 times higher than the resting value) observed during the rebreathing trial was mainly due to an increase in VT. This rise in ventilation was the highest ever reported in calves. Lobeline dose-dependently enhanced ventilation up to a threshold dose of 0.25 mg/kg, which always produced a maximal response. This maximal response (3.7 times higher than the resting value), reflecting both an increase in fR and VT, was reproducible at an interval of 12 h and was highly correlated with that observed during the rebreathing trial (R = 0.98, P< 0.001). These results suggest that: (1) rebreathing trial is a reliable method to induce and measure maximal ventilation in calves; and (2) lobeline administration (0.25 mg/kg) is a reliable means of accurately estimating this variable. Lobeline administration, unlike the rebreathing trial, is safe and easy to standardize, and the test therefore seems to be the preferred way of studying maximal ventilation in calves. [less ▲]

in Veterinary Record : Journal of the British Veterinary Association (1998), 143(7), 196-8

A three-year-old male golden retriever had had progressive dyspnoea, exercise intolerance, stridor, and a modified bark for five months. A mass 2 cm in diameter was present dorsal to the right side of the ... [more ▼]

A three-year-old male golden retriever had had progressive dyspnoea, exercise intolerance, stridor, and a modified bark for five months. A mass 2 cm in diameter was present dorsal to the right side of the larynx. Histological examination revealed cross-striations in some elongated cells, consistent with a diagnosis of rhabdomyoma, a diagnosis which was confirmed by positive immunohistochemical staining for myoglobin and desmin. The mass could not be removed without total laryngectomy and a permanent tracheostomy and the dog was euthanased. [less ▲]

in Veterinary Record : Journal of the British Veterinary Association (1997), 141(7), 168-172

The objectives of this study were to determine whether the infusion of platelet-activating factor would modify bovine pulmonary function, heart rate and platelet count and whether any such modifications ... [more ▼]

The objectives of this study were to determine whether the infusion of platelet-activating factor would modify bovine pulmonary function, heart rate and platelet count and whether any such modifications could be antagonised by the prior intravenous injection of a specific antagonist (WEB 2086). In saline-pretreated calves, the respiratory rate, total lung resistance (RL) and maximal changes in transpulmonary pressure (delta Ptp) were significantly increased whereas lung dynamic compliance (CLdyn), tidal volume (VT), platelet count and heart rate were significantly decreased. The changes in RL, CLdyn, VT and delta Ptp were abolished by pretreatment with WEB 2086, whereas respiratory rate remained significantly increased to 125 per cent of the baseline value, but less than in the saline-pretreated calves in which it was 250 per cent of the baseline value. [less ▲]

The effects of an acute non-isocapnic hypoxia on ventilation and pulmonary mechanics were investigated in 6 healthy unsedated Holstein-Friesian (HF) calves and in 7 double-muscled calves of the Belgian ... [more ▼]

The effects of an acute non-isocapnic hypoxia on ventilation and pulmonary mechanics were investigated in 6 healthy unsedated Holstein-Friesian (HF) calves and in 7 double-muscled calves of the Belgian White and Blue (BWB) breed known to develop more severe hypoxemia during exercise and respiratory diseases. Data were collected at 1 min intervals throughout the following protocol: breathing air (FIO2 = 21%), then breathing hypoxic gas mixture (FIO2 = 10%) for 5 min, and, finally, breathing air again for 5 min of recovery. Arterial blood was sampled at rest and at the 4th min of hypoxia for blood gas analysis. In HF and BWB calves, hypoxia induced a significant increase in tidal and minute volume, but did not change respiratory rate, dynamic lung compliance and total pulmonary resistance. However, with regard to their ventilation during normoxia at rest, BWB calves showed a comparatively greater rise in ventilation than HF calves during the first 4 min of hypoxia. On the contrary, by the 5th minute of hypoxia, ventilation of BWB calves declined to the normoxic level while HF calves largely sustained hyperventilation. This hypoxic ventilatory depression in BWB calves could be explained by the proportionately greater initial increase in ventilation. It was concluded that BWB calves supported this hypoxic challenge less easily than HF calves. [less ▲]

OBJECTIVE: To assess the peripheral chemoreceptor-induced ventilatory response to single tidal-breath CO2 (SB CO2) tests, compared with eructations, in 2 breeds of calves. ANIMALS: 13 conscious unsedated Holstein-Friesian and 8 Belgian White and Blue hypermuscled calves. PROCEDURE: An SB of +/- 50% CO2 in equal parts of O2 and N2 was inhaled. Ventilatory response was determined from the increase in ventilation (delta Ve) during the first 20 seconds after the test breath or eructation and from the difference in end-tidal PCO2 between the stimulus and preceding control breaths. RESULTS: Because no difference was found between the 2 breeds of calves, all data were pooled. The increase in Ve peaked during the fifth breath after the SB CO2 test on average, corresponding to a delay of 12.4 seconds. The SB CO2 responses ranged from 0.037 to 0.151 L/min.mm of Hg.m2, with a mean +/- SD of 0.082 +/- 0.032 L/min.mm of Hg.m2 for all calves. The SB CO2 tests, similar to eructations, modified the breathing pattern significantly and in the same direction, by principally shortening expiratory time and increasing mean inspiratory flow. After eructations, Ve peak increase was more important for lower difference in end-tidal PCO2 between the stimulus and preceding control breaths and took place more rapidly than after SB CO2 tests. Accordingly, eructation responses were more marked than SB CO2 responses and averaged 0.925 +/- 0.276 L/min.mm of Hg.m2. CONCLUSIONS AND CLINICAL RELEVANCE: In cattle, the pattern of breathing and ventilation under basal conditions is characterized by a cyclic variability coupled to eructation. [less ▲]

The in vivo ability of the specific PAF-antagonist WEB 2086, a thienotriazolodiazepine, to inhibit platelet-activating factor (PAF) in cattle was investigated by in vitro determination of platelet ... [more ▼]

The in vivo ability of the specific PAF-antagonist WEB 2086, a thienotriazolodiazepine, to inhibit platelet-activating factor (PAF) in cattle was investigated by in vitro determination of platelet aggregation curves. WEB 2086 was infused intravenously into a group of 5 healthy male Friesian calves in a dose of 3 mg/kg over 1 min. The resultant inhibition peaked between 30 min and 1 h after administration of WEB 2086. The inhibition was significantly reduced after 3 h and became non-significant after 6 h, but maximal pre-treatment aggregation had not been restored by 24 h after the injection of WEB 2086. These results confirm previous results obtained in vitro and suggest that WEB 2086 is a potent antagonist of PAF activity in calves. They also suggest that further clinical studies with WEB 2086 in cattle are desirable. [less ▲]